Gold(I)-Catalyzed Asymmetric Cyclizations and Cycloadditions of Heteroatom-Substituted Alkynes with Alkenes

Identifier:  TDX:4450

Handle: https://hdl.handle.net/20.500.11797/TDX4450

Authors:  Cataffo, Andrea

Abstract:
Gold(I)-catalyzed transformations are widely used for constructing complex molecular structures under mild conditions. Our research focused on asymmetric activation of heteroatom-substituted alkynes towards alkenes to yield cyclic compounds. We first developed two strategies for stereoselective gold(I)-catalyzed cyclizations of 1,n-enynes using chiral auxiliaries: we achieved a stereoselective cascade cyclization of 1,5-enynamides using Oppolzer camphorsultam, resulting in enantioenriched spirocyclic ketones via a one-pot cyclization-hydrolysis sequence; then, the stereoselective alkoxycyclization of 1,6-enynamides was directed by an Evans-type oxazolidinone, yielding enantioenriched β-tetralones after a reduction-hydrolysis sequence. DFT studies furnished insights on the stereoinduction operated by the chiral auxiliary. We then developed a protocol for the synthesis of cyclobutenes and cyclobutanones, important scaffolds in natural products and organic synthesis: gold(I)-catalyzed [2+2] cycloaddition of alkenes with terminal ynol ethers afforded cyclobutyl enol ethers with good yields and regioselectivities, which could be hydrolyzed or brominated to yield cyclobutanones. Finally, we also developed the first enantioselective gold(I)-catalyzed alkoxycyclization of 1-bromo-1,6-enynes, resulting in enantioenriched 5-membered-ring vinyl bromides that could be further derivatized. Both experimental and theoretical studies revealed an in-cycle racemization process via a reversible 1,2-H shift, providing a new understanding of gold(I)-catalyzed alkoxycyclizations.